Interferon alfa for chronic hepatitis C infection

Abstract

Thierry Poynard and colleagues (Oct 31, p 1426)1Poynard T Marcellin P Lee SS et al.Randomised trial of interferon alfa-2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alfa-2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus.Lancet. 1998; 352: 1426-1432Summary Full Text Full Text PDF PubMed Scopus (2400) Google Scholar state that interferon alfa has “an acceptable safety profile”. In so doing, they fail to mention the existence of some common and potentially serious adverse effects of interferon alfa of which all clinicians considering the initiation of this drug should be aware. Autoimmune thyroid disease has been shown by Gisslinger and co-workers2Gisslinger H Gilly B Woloszczuk W et al.Thyroid autoimmunity and hypothyroidism during long-term treatment with recombinant interferon-alpha.Clin Exp Immunol. 1992; 90: 363-367Crossref PubMed Scopus (123) Google Scholar to develop in more than 20% of patients on long-term treatment with interferon alfa. Many patients with this complication develop positive thyroid autoantibodies, especially thyroid microsome antibody,2Gisslinger H Gilly B Woloszczuk W et al.Thyroid autoimmunity and hypothyroidism during long-term treatment with recombinant interferon-alpha.Clin Exp Immunol. 1992; 90: 363-367Crossref PubMed Scopus (123) Google Scholar after starting interferon alfa. Up to 50% of such patients in a study by Baudin et al3Baudin E Marcellin P Pouteau M et al.Reversibility of thyroid dysfunction induced by recombinant alpha interferon in chronic hepatitis C.Clin Endocrinol. 1993; 39: 657-661Crossref PubMed Scopus (144) Google Scholar had previously tested negative for thyroid autoantibodies before such treatment. It is noteworthy that the development of autoimmune thyroid disease as a result of this drug may be reversible since all patients in Baudin's study3Baudin E Marcellin P Pouteau M et al.Reversibility of thyroid dysfunction induced by recombinant alpha interferon in chronic hepatitis C.Clin Endocrinol. 1993; 39: 657-661Crossref PubMed Scopus (144) Google Scholar had normal thyroid function within 2 years of stopping therapy. The neurotoxic effects of interferon alfa are also well recognised. In fact, psychiatric adverse effects developed in 17% of patients given this drug for chronic viral hepatitis.4Renault PF Hoofnagle JH Park Y et al.Psychiatric complications of long-term interferon-alfa therapy.Arch Intern Med. 1987; 147: 1577-1580Crossref PubMed Scopus (405) Google Scholar In this study, psychiatric side-effects were the most frequent reason for discontinuation of interferon alfa. These effects usually took place after 1–3 months of treatment and invariably resolved once therapy was stopped. Patients receiving the highest dose of interferon alfa, who also had mild hepatitis, tended to develop affective disorders or personality changes. Delirium tended to arise in patients with severe hepatitis who had previous evidence of organic brain injury or dysfunction or previous alcohol or drug abuse. Two delirious patients also showed a pronounced urge to commit suicide, one patient stating that he had injected interferon alfa intravenously in an attempt to kill himself. Suicidal thoughts as a result of interferon alfa therapy, including completed suicide, has also been reported by other workers. A recent case in which a patient on chronic interferon alfa therapy presented with concurrent psychiatric disorder and thyroid dysfunction5Kingsley D, Case Report: Interferon-alpha induced “Tertiary Mania”. Hospital Med (in press).Google Scholar links both thyroid and psychiatric syndromes and emphasises the difficulty faced in reaching a diagnosis of “tertiary” mania caused by autoimmune hypothyroidism induced by interferon alfa. Although this drug is a successful and increasingly popular treatment for various clinical conditions, clinicians considering its use should be aware of these adverse effects. The exclusion for Poynard's study of patients with preexisting psychiatric conditions and autoimmune-type disease may have led to under-reporting of these adverse effects. In all cases in whom interferon alfa is being considered, thyroid function and autoantibody status should be established before starting therapy, and then monitored regularly during treatment. It is also recommended that in patients with a history of psychiatric illness, especially those with a history of suicidal ideation, interferon alfa should only be used with careful monitoring of the patient's mental state. Interferon alfa for chronic hepatitis C infectionAuthors' reply Full-Text PDF